Neuromuscular

Neuromas 1,2

Neuromas (Sural nerve)
  Aberant fascicles
    Minifascicles
  Nerve branch
  Regenerated axon clusters
Neuroma (C5 root): Distal to lesion
  Axon sprouts
    GAP43
  Axons
  Perineurium
Also see
  Blocked axon regeneration
  Axon swellings

Regeneration: Aberrant Fascicles


H&E stain
Minifascicles
  Varied sizes & orientations

H&E stain

Gomori trichrome stain
Post-regeneration: Small fascicles with varied size and orientations

Gomori trichrome stain
Neuroma: Multiple small fascicles containing myelinated axons

VvG stain

Neurofilament stain
Neuroma: Small minifascicles in epineurium
  Contain myelinated & unmyelinated axons

Neurofilament stain

Regenerated Axon Clusters within Neuroma

Neuroma
  Varied sizes & orientations of axon clusters (fascicles)
Neuroma
  Axons in fascicles tend to be thinly myelinated for their size
  Small minifascicles contain 1 to 30 myelinated axons
Neuroma
Neuroma
  Varied numbers of myelinated & non-myelinated axons in fascicles
  Varied numbers of axons in fascicles
Neuroma
  Several small fascicles separated by connective tissue
  Each fascicle is surrounded by perineurium, 1 or several layers

From: R Schmidt
Minifascicles
  Contents
    Thinly myelinated axons
    Clusters of Schwann cell processes (Büngner bands)
    Collagen
  Surrounded by
    Perimysial cell/Fibroblast process

From: R Schmidt

From: R Schmidt
Minifascicles
  Contents
    Thinly myelinated axons
    Clusters of Schwann cell processes (Büngner bands)
    Collagen
  Surrounded by
    Perimysial cell/Fibroblast process

From: R Schmidt
Clusters of thinly myelinated axons

From: R Schmidt
Neuroma: Minifascicles
Small minifascicles: Contain 1 or 2 thinly myelinated axons (Top)
Fascicle with normal organization (Bottom left)

Toluidine blue stain
Small minifascicles: Contain thinly myelinated axons

Neuroma: Origin

Neuroma: Nerve branch originating from normal fascicle
Normal nerve fascicle (Left); Fascicles with varied size and orientations (Right)

VvG stain

VvG stain

Gomori trichrome stain

Neuroma (Region along nerve at, or distal to, lesion): C5 Root

Neuroma (C5 root)
  Morphology
  Axon sprouts
    GAP43
  Perineurium

H&E stain
Nerve at, or distal to, region of damage: Regions
  Persisting nerve structures (Arrows)
    Cellular: Heterogeneous region; Cells present in clusters
    Contains clusters of myelinated axons
  Surrounding connective tissue: Contains aberrantly regenerated axons
    Connective Tissue Structure: Moderately dense to pale
    Aberrant myelinated axons: Single & Clustered (Below)

VvG stain

Neurofilament stain
Neuroma (Right): Cluster of axons
Axon sprouts: Scattered single axons grow into connective tissue (Left)

NCAM stain

H&E stain
Neuroma (Right): Cluster of axons with extension into connective tissue
Axon sprouts: Scattered single axons grow into connective tissue (Left)

H&E stain

Gomori Trichrome stain
Neuroma (Right): Cluster of axons, sopme myelinated (Red) with extension into connective tissue
Axon sprouts: Scattered single axons grow into connective tissue (Left)

H&E stain
Neuroma (Top): Cluster of axons with extension into connective tissue
Axon sprouts: Scattered single axons grow into connective tissue (Bottom)

H&E stain
Neuroma (Above): Cluster of axons with extension into connective tissue
Axon sprouts: Scattered single axons grow into connective tissue (Below)

H&E stain

Neuroma: Axons & Schwann cells


Neurofilament (Green); NCAM (Red)
NCAM
  Present in Schwann cells around most axons in Neuroma (Left) & surrounding axon sprouts (Right)

Neurofilament (Green); P0 (Red)
P0 protein
  Present in Schwann cells around some, but not all, axons in & around Neuroma

Neurofilament (Green); P0 (Red)

Neurofilament (Green); MBP (Red)
Immature Schwann Cells/Myelin: Express MBP in cells on axons with thin, or no, myelin
  Small & Intermediate-sized axons
    Many have associated MBP+ Schwann cells (Yellow)

Neurofilament (Green); MBP (Red)

Neurofilament (Green); GAP43 (Red)
GAP43
  Axons in Neuroma: Contain GAP43 (Yellow) more in peripheral than central areas

Neurofilament (Green); GAP43 (Red)

Axon Sprouts


From: R Schmidt
Regenerating Axons
  Clusters of processes
  2 types of contents
    Tubulovesicular profiles
      Densely distributed in axon processes
      Compare to: Axons, large & proximal to nerve lesion
    Organelles, including many mitochondria
  No surrounding Schwann cell cytoplasm

From: R Schmidt

From: R Schmidt
Regenerating Axons
  Cluster of moderate-sized processes
  All contain mainly Tubulovesicular profiles
    Densely distributed
  No surrounding Schwann cell cytoplasm

From: R Schmidt

From: R Schmidt
Regenerating Axons
  Cluster of processes
  Tubulovesicular profiles surrounded by Organelles, including many mitochondria
  No surrounding Schwann cell cytoplasm

From: R Schmidt

From: R Schmidt
Regenerating Axons
  Mixed contents: Tubulovesicular profiles & Organelles
  No surrounding Schwann cell cytoplasm

From: R Schmidt

Neuroma: New Perineurial sheaths formed around small clusters of axons


EMA (Green): P0 (Red)
Perineurium in & around Neuroma
  EMA (Green) stains scattered perineurial cells & rings of perineurium around small, aberrant regenerated axon (myelin) clusters (Red)
  Compare to: Nerve proximal to damage region

EMA (Green): P0 (Red)
Return to Neuromuscular Home Page
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References
1. J Am Acad Orthop Surg 2025;33:178-186
2. PLoS One 2018;13:e0200548

6/13/2025
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